3-((3,4-dicyanophenyl)sulfonyl)-N-(2-hydroxypropyl)propane-1-sulfonamide

Eye irritation

Administrative data

Endpoint:

eye irritation: in vivo

Remarks:

in vivo, existing study

Type of information:

experimental study

Adequacy of study:

key study

Study period:

The study was performed between 24th May and 4th June 2010. The final report was issued 27th August 2010.

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2010

Report date:

2000

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

EU Method B.5 (Acute Toxicity: Eye Irritation / Corrosion)

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Test material

Test material information

Constituent 1

Reference substance name:

3-((3,4-Dicyanophenyl)sulfonyl)-N-(2-hydroxypropyl)propane-1-sulfonamide

Cas Number:

569316-81-0

Molecular formula:

C14H17N3O5S2

IUPAC Name:

3-((3,4-Dicyanophenyl)sulfonyl)-N-(2-hydroxypropyl)propane-1-sulfonamide

Test material form:

solid

Test animals / tissue source

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

Two New Zealand White rabbits were supplied by a reputable UK laboratory. At the start of the study the animals weighed 2.22 or 2.29 kg and were twelve to twenty weeks old. After an acclimatisation period of at least five days each animal was given a number unique within the study which was written with a black indelible marker-pen on the inner surface of the ear and on the cage label.

The animals were individually housed in suspended cages. Free access to mains drinking water and food (2030 Teklad Global Rabbit diet) was allowed throughout the study. The diet and drinking water were considered not to contain any contaminant of a level that might have affected the purpose or integrity of the study

The temperature and relative humidity were set to achieve limits of 17 to 23°C and 30 to 70% respectively. Any occasional deviations from these targets were considered not to have affected the purpose or integrity of the study. The rate of air exchange was at least fifteen changes per hour and the lighting was controlled by a time switch to give twelve hours continuous light (06:00 to 18:00) and twelve hours darkness.The animals were provided with environmental enrichment items which were considered not to contain any contaminant of a level that might have affected the purpose or integrity of the study.

Test system

Vehicle:

unchanged (no vehicle)

Controls:

no

Details on study design:

Immediately before the start of the test, both eyes of the provisionally selected test rabbits were examined for evidence of ocular irritation or defect with the aid of a light source from a standard ophthalmoscope. Only animals free of ocular damage were used.

Initially, a single rabbit was treated. A volume of 0.1 ml of the test material, which was found to weigh approximately 66 mg (as measured by gently compacting the required volume into an adapted syringe) was placed into the conjunctival sac of the right eye, by gently pulling the lower lid away from the eyeball. The upper and lower eyelids were held together for about one second immediately after treatment, to prevent loss of the test material, and then released. The left eye remained untreated and was used for control purposes. Immediately after administration of the test material, an assessment of the initial pain reaction was made according to the six point scale.

After consideration of the ocular responses produced in the first treated animal, a second animal was treated. In order to minimise pain on application of the test material, one drop of local anaesthetic (Tetracaine hydrochloride 0.5%, Chauvin Pharmaceuticals, Romford, Essex, UK) was instilled into both eyes of the second animal 1 to 2 minutes before treatment.

Assessment of ocular damage lirritation was made approximately 1 hour and 24, 48 and 72 hours following treatment, according to the numerical evaluation Draize (from Draize J H (1977) "Dermal and Eye Toxicity Tests" In: Principles and Procedures for Evaluating the Toxicity of Household Substances, National Academy of Sciences, Washington DC p.48 to 49). Any other ocular effects were also noted. Examination of the eye was facilitated by the use of the light source from a standard ophthalmoscope. Any clinical signs of toxicity, if present, were also recorded.

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

cornea opacity score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0

Max. score:

0

Reversibility:

other: Not applicable as no effect

Results 2

Irritation parameter:

cornea opacity score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0

Max. score:

0

Reversibility:

other: Not applicable as no effect

Results 3

Irritation parameter:

iris score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0

Max. score:

0

Reversibility:

other: Not applicable as no effect

Results 4

Irritation parameter:

iris score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0

Max. score:

0

Reversibility:

other: Not applicable as no effect

Results 5

Irritation parameter:

conjunctivae score

Basis:

animal #1

Time point:

24 h

Score:

1

Max. score:

2

Reversibility:

fully reversible within:

Remarks:

48 hr

Results 6

Irritation parameter:

conjunctivae score

Basis:

animal #2

Time point:

24 h

Score:

1

Max. score:

2

Reversibility:

fully reversible within:

Remarks:

48hr

Irritant / corrosive response data:

No corneal or iridial effects were noted during the study.
Reversibility of conjunctival irritation observed within 48 hours.

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

The test material produced a maximum group mean score of 10.0 and was classified as a minimal irritant (Class 3 on a 1 to 8 scale) to the rabbit eye according to a modified Kay and Calandra classification system.

Executive summary:

Introduction

The study was performed to assess the irritancy potential of the test material to the eye of the New Zealand White rabbit. The method was designed to meet the requirements of the following: OECD Guidelines for the Testing of Chemicals No. 405 "Acute Eye Irritation/Corrosion" (adopted 24 April 2002) and Method B5 Acute Toxicity (Eye Irritation) of Commission Regulation (EC) No. 44012008.

Result

A single application of the test material to the non-irrigated eye of two rabbits produced moderate conjunctival irritation. Both treated eyes appeared normal at the 48-hour observation.

Conclusion

The test material produced a maximum group mean score of 10.0 and was classified as a minimal irritant (Class 3 on a I to 8 scale) to the rabbit eye according to a modified Kay and Calandra classification system.